Fecal Fat Points to Early Presence of Colorectal Cancer

Colorectal cancer (CRC) remains a leading cause of cancer mortality worldwide, and therefore more accessible screening tests are urgently needed to identify early-stage lesions. Colonoscopy, for example, is a known lifesaver but is costly and unappealing to many people who might otherwise undergo testing.

The use of ultrasensitive, high-speed technology has identified a suite of molecules in the feces of mice that signifies the presence of precancerous polyps and this "metabolic fingerprint" matches changes in both mouse and human colon tumor tissues and suggests a potential new diagnostic tool for early detection of colorectal cancer in a clinical setting.

Scientists at the Washington State University (Pullman, WA, USA) and their colleagues hypothesized that highly sensitive, metabolic profile analysis of stool samples will identify metabolites associated with early-stage lesions and could serve as a noninvasive screening test. They first identified metabolic products from normal colon tissue in both humans and mice and then compared this normal profile to that found in cancerous colon tissues from humans and research mice with polyps in their colons that mimic those in humans.

The investigators applied travelling wave ion mobility mass spectrometry (TWIMMS) coupled with ultra-performance liquid chromatography (UPLC) to investigate metabolic aberrations in stool samples in a transgenic model of pre-malignant polyposis aberrantly expressing the gene encoding the high mobility group A (Hmga1) chromatin remodeling protein. Metabolic extract samples were analyzed by use of a Synapt G2-TWIMMS instrument and chromatographic pre-separation was achieved by use of an ACQUITY UPLC instrument and eluent was introduced to the TWIMMS system via electrospray ionization (ESI) (Waters Corporation, Manchester, UK).

The scientists found that the fecal metabolome of Hmga1 mice is distinct from that of control mice and includes metabolites previously identified in human CRC. Significant alterations were observed in fatty acid metabolites and metabolites associated with bile acids (hypoxanthine xanthine, taurine) in Hmga1 mice compared to controls. Surprisingly, a marked increase in the levels of distinctive short, arginine-enriched, tetra-peptide fragments was observed in the transgenic mice.

Herbert H Hill, Jr, PhD, a professor of Chemistry and senior author of the study, said, “The feces was not exactly the same as the tissue samples, but it had a lot of similarities to the tissue. We found the lipids and fatty acids were changing, and there were also changes in the amino acids. The exciting part is being able to see differences in the stool. This could lead to a noninvasive, more comprehensive early-warning detection method for colorectal cancer.” The study was published on October 4, 2016, in the Journal of Proteome Research.

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